2-Decarboxy-2-hydroxymethyl-ω-phenoxy-PGD analogs

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl is replaced by a primary alcohol. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 647,357, filed Jan. 8, 1976, now issued as U.S. Pat. No. 4,055,602.

The present invention relates to prostaglandin analogs, for which the essential material constituting disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,055,602, issued Oct. 25, 1977. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## WHEREIN R₈ is hydrogen or hydroxy; WHEREIN Y is trans-CH═CH--;wherein M₁ is ##STR2## wherein R₅ is hydrogen or hydroxy; WHEREIN L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen or methyl, being the same or different; Wherein Z₂ is Cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --; cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --; or --(CH₂)₃ --(CH₂)_(g) --CF₂ --; wherein g is one, 2, or 3; and Wherein s is zero, one, 2, or 3 and T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl.
 2. A compound according to claim 1, wherein R₈ is hydrogen.
 3. A compound according to claim 2, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 4. A compound according to claim 3, wherein Z₂ is cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 5. A compound according to claim 4, wherein g is one.
 6. A compound according to claim 5, wherein at least one of R₃ and R₄ is methyl.
 7. A compound according to claim 6, wherein R₃ and R₄ are both methyl.
 8. A compound according to claim 7, wherein R₅ is methyl.
 9. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-9-deoxy-PGD₂, a compound according to claim
 8. 10. A compound according to claim 7, wherein R₅ is hydrogen.
 11. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-methyl-16-phenoxy-18,19,20-trinor-9-deoxy-PGD₂, a compound according to claim
 10. 12. A compound according to claim 5, wherein R₃ and R₄ are both hydrogen.
 13. A compound according to claim 12, wherein R₅ is methyl.
 14. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-16-phenoxy-17,19,19,20-tetranor-9-deoxy-PGD₂, a compound according to claim
 13. 15. A compound according to claim 12, wherein R₅ is hydrogen.
 16. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-phenoxy-17,18,19,20-tetranor-9-deoxy-PGD₂, a compound according to claim
 15. 17. A compound according to claim 3, wherein Z₂ is --(CH₂)₃ --(CH₂)_(g) --CF₂ --.
 18. A compound according to claim 17, wherein g is one.
 19. A compound according to claim 18, wherein at least one of R₃ and R₄ is methyl.
 20. A compound according to claim 19, wherein R₃ and R₄ are both methyl.
 21. A compound according to claim 20, wherein R₅ is methyl.
 22. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-9-deoxy-PGD₁, a compound according to claim
 21. 23. A compound according to claim 20, wherein R₅ is hydrogen.
 24. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-methyl-16-phenoxy-18,19,20-trinor-9-deoxy-PGD₁, a compound according to claim
 23. 25. A compound according to claim 18, wherein R₃ and R₄ are both hydrogen.
 26. A compound according to claim 25, wherein R₅ is methyl.
 27. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-16-phenoxy-17,19,19,20-tetranor-9-deoxy-PGD₁, a compound according to claim
 26. 28. A compound according to claim 25, wherein R₅ is hydrogen.
 29. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-phenoxy-17,19,19,20-tetranor-9-deoxy-PGD₁, a compound according to claim
 28. 30. A compound according to claim 3, wherein Z₂ is cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 31. A compound according to claim 30, wherein g is one.
 32. A compound according to claim 31, wherein at least one of R₃ and R₄ is methyl.
 33. A compound according to claim 32, wherein R₃ and R₄ are both methyl.
 34. A compound according to claim 33, wherein R₅ is methyl.
 35. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-9-deoxy-PGD₁, a compound according to claim
 34. 36. A compound according to claim 33, wherein R₅ is hydrogen.
 37. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16-methyl-16-phenoxy-18,19,20-trinor-9-deoxy-PGD₁, a compound according to claim
 36. 38. A compound according to claim 31, wherein R₃ and R₄ are both hydrogen.
 39. A compound according to claim 38, wherein R₅ is methyl.
 40. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15-methyl-16-phenoxy-17,18,19,20-tetranor-9-deoxy-PGD₁, a compound according to claim
 39. 41. A compound according to claim 38, wherein R₅ is hydrogen.
 42. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16-phenoxy-17,19,19,20-tetranor-9-deoxy-PGD₁, a compound according to claim
 41. 43. A compound according to claim 1, wherein R₈ is hydroxy.
 44. A compound according to claim 43, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 45. A compound according to claim 44, wherein Z₂ is cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 46. A compound according to claim 45, wherein g is one.
 47. A compound according to claim 46, wherein at least one of R₃ and R₄ is methyl.
 48. A compound according to claim 47, wherein R₃ and R₄ are both methyl.
 49. A compound according to claim 48, wherein R₅ is methyl.
 50. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-PGD₂, a compound according to claim
 49. 51. A compound according to claim 48, wherein R₅ is hydrogen.
 52. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-methyl-16-phenoxy-18,19,20-trinor-PGD₂, a compound according to claim
 51. 53. A compound according to claim 46, wherein R₃ and R₄ are both hydrogen.
 54. A compound according to claim 53, wherein R₅ is methyl.
 55. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-16-phenoxy-17,18,19,20-tetranor-PGD₂, a compound according to claim
 54. 56. A compound according to claim 53, wherein R₅ is hydrogen.
 57. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-phenoxy-17,18,19,20-tetranor-PGD₂, a compound according to claim
 56. 58. A compound according to claim 44, wherein Z₂ is --(CH₂)₃ --(CH₂)_(g) --CF₂ --.
 59. A compound according to claim 58, wherein g is one.
 60. A compound according to claim 59, wherein at least one of R₃ and R₄ is methyl.
 61. A compound according to claim 60, wherein R₃ and R₄ are both methyl.
 62. A compound according to claim 61, wherein R₅ is methyl.
 63. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-PGD₁, a compound according to claim
 62. 64. A compound according to claim 61, wherein R₅ is hydrogen.
 65. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-methyl-16-phenoxy-18,19,20-trinor-PGD₁, a compound according to claim
 64. 66. A compound according to claim 60, wherein R₃ and R₄ are both hydrogen.
 67. A compound according to claim 66, wherein R₅ is methyl.
 68. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-16-phenoxy-17,18,19,20-tetranor-PGD₁, a compound according to claim
 67. 69. A compound according to claim 66, wherein R₅ is hydrogen.
 70. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16-phenoxy-17,19,19,20-tetranor-PGD₁, a compound according to claim
 69. 71. A compound according to claim 44, wherein Z₂ is cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 72. A compound according to claim 71, wherein g is one.
 73. A compound according to claim 72, wherein at least one of R₃ and R₄ is methyl.
 74. A compound according to claim 73, wherein R₃ and R₄ are both methyl.
 75. A compound according to claim 74, wherein R₅ is methyl.
 76. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-PGD₁, a compound according to claim
 75. 77. A compound according to claim 74, wherein R₅ is hydrogen.
 78. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16-methyl-16-phenoxy-18,19,20-trinor-PGD₁, a compound according to claim
 77. 79. A compound according to claim 72, wherein R₃ and R₄ are both hydrogen.
 80. A compound according to claim 79, wherein R₅ is methyl.
 81. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15-methyl-16-phenoxy-17,18,19,20-tetranor-PGD₁, a compound according to claim
 80. 82. A compound according to claim 79, wherein R₅ is hydrogen.
 83. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16-phenoxy-17,18,19,20-tetranor-PGD₁, a compound according to claim
 82. 